Orexin-A (OX-A) and orexin-B (OX-B) (hypocretin 1 and hypocretin 2) are synthesized in neurons of the perifornical, dorsomedial, lateral, and posterior hypothalamus. The locus coeruleus (LC) receives the densest extrahypothalamic projections of the orexin (OX) system. Recent evidence suggests that descending projections of the LC have a facilitatory role in the regulation of muscle tone. The pontine inhibitory area (PIA), located ventral to LC, receives a moderate OX projection and participates in the suppression of muscle tone in rapid-eye-movement sleep. We have examined the role of OX-A and -B in muscle-tone control using microinjections (0.1 microM to 1 mM, 0.2 microl) into the LC and PIA in decerebrate rats. OX-A and -B microinjections into the LC produced ipsi- or bilateral hindlimb muscle-tone facilitation. The activity of LC units was correlated with the extent of hindlimb muscle-tone facilitation after OX microinjections (100 microM, 1 microl) into fourth ventricle. Microinjections of OX-A and -B into the PIA produced muscle-tone inhibition. We did not observe any significant difference in the effect of OX-A and -B on muscle tone at either site. Our data suggest that OX release activates LC units and increases noradrenergic tonus in the CNS. Moreover, OX-A and -B may also regulate the activity of pontine cholinoceptive and cholinergic neurons participating in muscle-tone suppression. Loss of OX function may therefore disturb both facilitatory and inhibitory motor processes.